The overall objective of this research is to improve host defense mechanisms as a means for controlling infections in surgical patients. This will be accomplished through several broadly specific aims: 1) determination of the role of intestinal bacteria and/or endotoxin in the hypermetabolic response following burn injury; 2) determination of the optimal dietary composition for nutritional support of septic subjects; 3) a study of the effect of burn and/or infection on the synthesis and release of specific macrophage products and their effects on host defense; 4) continuation of testing promising immunomodulators to determine their role in improving resistance to infection with different bacteria in normal and burned animal models with examination of the mechanism of action; 5) examination of leukocyte subpopulations and surface receptors in burn patients and normal individuals; 6) testing immunomodulators in single and multiple combinations with or without standard antibiotic therapy in burned animals receiving a chronic infectious challenge. The standard nutritional model in animals will involve placement of a gastrostomy tube approximately one week prior to either burn injury or implantation of a bacterial laden sponge entraped in a fibrin clot and implanted into the peritoneal cavity. A clinical study will be done to determine the benefit of enteral feeding immediately postburn. Leukocyte subpopulations will be studied using flow cytometry to detect the presence and density of specific surface receptors and to define subpopulation-function interrelationships. Both presently available and newly developed monoclonal antibodies will be used in these studies for detection in these surface markers. Finally, alterations in mediators produced by macrophages from animals after burn, sepsis or immunomodulator treatment will be studied. The expected result of the proposed research will be that an entirely new diet will be formulated for optimal nutritional support in subjects with severe bacterial infection, new immunomodulators and combinations of immune modulators will be identified which will prove more effective for preventing and treating infection in the immunodepressed or infected subject than is now possible, and a better understanding of the mechanism whereby host defense can be improved will be obtained.